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HUMANS: The next Human Genome Project: Our microbes

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TITLE:  The next Human Genome Project: Our microbes
SOURCE: Technology Review, USA
AUTHOR: Emily Singer
DATE:   02.05.2007

The next Human Genome Project: Our microbes

A proposed project to sequence the microorganisms that inhabit our
bodies could have a huge impact on human health.

Much as we might like to ignore them, microbes have colonized almost
every inch of our bodies, living in our mouths, skin, lungs, and gut.
Indeed, the human body has 10 times as many microbial cells as human
cells. They're a vital part of our health, breaking down otherwise
indigestible foods, making essential vitamins, and even shaping our
immune system. Recent research suggests that microbes play a role in
diseases, such as ulcers, heart disease, and obesity.

While microbes make up such an intimate part of us, most of our
microbial inhabitants remain a mystery. The bacteria in the human body
are very difficult to study, since only about 1 percent of them can be
grown in the lab. Now a proposed new project to sequence all our
microbial residents could change that.

"This is completely unexplored territory that is likely to have a large
impact on our understanding of human health and disease," says George
Weinstock, codirector of the Human Sequencing Center at the Baylor
College of Medicine, in Houston. "We hadn't been able to approach it
because of the scale of the problem. But now we are finally able to open
that door."

Thanks to ever-improving methods to sequence DNA, scientists can now
analyze the genomes of entire microbial communities, a field known as
metagenomics. By comparing microbial communities in people of different
ages, origins, and health statuses, researchers hope to find out
precisely how microorganisms prevent or increase risk for certain
diseases and whether they can be manipulated to improve health.

Several metagenomics projects are under way or have been completed,
including analysis of the microbes living in the human gut and on the
skin. But a true snapshot of our microbial menagerie will require a
massive effort, along the lines of the Human Genome Project. "Even
though a microbial genome is one-thousandth the size of the human
genome, the total number of microbial genes in [the human] body is much
greater than human genes because you have so many different species,"
says Weinstock.

The National Institutes of Health (NIH) is now considering such a
project. Metagenomics experts and government officials met last week to
determine if the proposal, dubbed the human microbiome, will become an
NIH "Roadmap" initiative. These NIH-wide programs identify major gaps in
biomedical research and provide financial support on a much larger scale
than typical grants. A final decision is expected this month.

"At the end of the day, we'll end up with another perspective on the
evolution of our species, our human-microbial selves," says Jeffrey
Gordon, a microbiologist at the Washington University School of
Medicine, in St. Louis.

Recent research from Gordon's lab hints at the potential public-health
impact of a clearer understanding of our microbial tenants. Gordon and
his colleagues have shown that obese people harbor different microbial
communities than lean people. And as obese people lost weight, their
microbes began to look more like their lean counterparts' microbes.

Researchers aren't yet sure what triggers the differences, but they
found in a similar study in mice that the microbial populations of obese
mice could more effectively release calories from food during digestion
than could microbes of their lean littermates.

While exciting, Gordon's research also illustrates the challenges of
cataloging microbes. To truly interpret the human microbiome, scientists
will need to look at the variation in microbial communities among many
people and a variety of populations. Complicating the problem is that,
while an individual's human genome is static, a person's microbial
composition--and thus his or her microbiome--fluctuates over time. So an
accurate picture of one person's microbiome could require multiple
resequencing efforts.

These types of studies could yield the biggest reward, revealing whether
different organisms are correlated with different health states. Gordon
and others hope that a microbial analysis will ultimately become a
routine part of medical exams, perhaps used to diagnose different diseases.

Scientists are still debating whether the microbiome will become a road-
map project, and if so, what the final goals of the project will be:
should they focus on generating complete sequences of dominant microbes,
for example, or devote equal energy to the complex task of studying
microbial variation?

In the meantime, microbiologists are getting ready. Three large
sequencing centers--at Baylor, the Broad Institute, and Washington
University--have garnered funding to sequence the genomes of a few of
the gut microorganisms that can be grown in the lab, which will be
crucial in later studies. Ultimately, says Gordon, "we'll get a much
more transcendent view of ourselves as a supraorganism with traits
acquired from our microbial partnerships."

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